Synaptic-like microvesicles of neuroendocrine cells originate from a novel compartment that is continuous with the plasma membrane and devoid of transferrin receptor

We have characterized the compartment from which synaptic-like microvesicles (SLMVs), the neuroendocrine counterpart of neuronal synaptic vesicles, originate. For this purpose we have exploited the previous observation that newly synthesized synaptophysin, a membrane marker of synaptic vesicles and SLMVs, is delivered to the latter organelles via the plasma membrane and an internal compartment. Specifically, synaptophysin was labeled by cell surface biotinylation of unstimulated PC12 cells at 18 degrees C, a condition which blocked the appearance of biotinylated synaptophysin in SLMVs and in which there appeared to be no significant exocytosis of SLMVs. The majority of synaptophysin labeled at 18 degrees C with the membrane-impermeant, cleavable sulfo-NHS-SS-biotin was still accessible to extracellularly added MesNa, a 150-D membrane-impermeant thiol-reducing agent, but not to the 68,000-D protein avidin. The SLMVs generated upon reversal of the temperature to 37 degrees C originated exclusively from the membranes containing the MesNa-accessible rather than the MesNa-protected population of synaptophysin molecules. Biogenesis of SLMVs from MesNa-accessible membranes was also observed after a short (2 min) biotinylation of synaptophysin at 37 degrees C followed by chase. In contrast to synaptophysin, transferrin receptor biotinylated at 18 degrees or 37 degrees C became rapidly inaccessible to MesNa. Immunofluorescence and immunogold electron microscopy of PC12 cells revealed, in addition to the previously described perinuclear endosome in which synaptophysin and transferrin receptor are colocalized, a sub-plasmalemmal tubulocisternal membrane system distinct from caveolin-positive caveolae that contained synaptophysin but little, if any, transferrin receptor. The latter synaptophysin was selectively visualized upon digitonin permeabilization and quantitatively extracted, despite paraformaldehyde fixation, by Triton X-100. Synaptophysin biotinylated at 18 degrees C was present in these subplasmalemmal membranes. We conclude that SLMVs originate from a novel compartment that is connected to the plasma membrane via a narrow membrane continuity and lacks transferrin receptor.     

Refinements in validity generalization methods: Implications for the situational specificity hypothesis.

Using a large database, this study examined 3 refinements of validity generalization procedures: (1) a more accurate procedure for correcting the residual standard deviation (SD) for range restriction to estimate SDp, (2) use of r? instead of study-observed rs in the formula for sampling error variance, and (3) removal of non-Pearson rs. The 1st procedure does not affect the amount of variance accounted for by artifacts. The addition of the 2nd and 3rd procedures increased the mean percentage of validity variance accounted for by artifacts from 70 to 82%, a 17% increase. The cumulative addition of all 3 procedures decreased the mean SDp estimate from .150 to .106, a 29% decrease. Six additional variance-producing artifacts were identified that could not be corrected for. In light of these it was concluded that the obtained estimates of mean SDp and mean validity variance accounted for were consistent with the hypothesis that the true mean SDp value is close to zero. These findings provide further evidence against the situational specificity hypothesis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The dimensions underlying perceived attitudes: Liberalism and concern for traditional values.

Two studies identified and labeled the dimensions that people use to judge others' attitudes. In the 1st study, 50 male and 50 female undergraduates viewed pairs of attitude statements drawn from 1 or 2 large sets. For each pair of statements, Ss judged whether or not a person who agreed with one statement in the pair would be likely to agree with the other. The dimensions of liberalism and traditional values were found to underlie perceived attitudes. Validity was confirmed in a 2nd study with 60 male and 60 female undergraduates who rated the characteristics of hypothetical people who agreed strongly with particular statements. Results suggest that there is a common structure to people's perceptions of others' attitudes. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Structure of Working Memory From 4 to 15 Years of Age.

The structure of working memory and its development across the childhood years were investigated in children 4-15 years of age. The children were given multiple assessments of each component of the A. D. Baddeley and G. Hitch (1974) working memory model. Broadly similar linear functions characterized performance on all measures as a function of age. From 6 years onward, a model consisting of 3 distinct but correlated factors corresponding to the working memory model provided a good fit to the data. The results indicate that the basic modular structure of working memory is present from 6 years of age and possibly earlier, with each component undergoing sizable expansion in functional capacity throughout the early and middle school years to adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.     

Outdoor attractancy of males ofMatsucoccus josephi (Homoptera: Matsucoccidae) andElatophilus hebraicus (Hemiptera: Anthocoridae) to synthetic female sex pheromone ofMatsucoccus josephi

The active component of the sex pheromone ofMatsucoccus josephi is (2E,6E,8E)-5,7-dimethyl-2,6,8-decatrien-4-one; the chemical is also a powerful kairomone of adult males and females of the bugElatophilus hebraicus the principal predator ofM. josephi. The presence of theZ isomer (2E,6Z,8E)-5,7-dimethyl-2,6,8-decatrien-4-one does not interfere with the attractancy of the activeE component forM. josephi males or the bug. Our results show a clear dose-response between trap catch ofM. josephi males andE. hebraicus. Conversely, increasing amounts of theZ isomer in the mixture did not affect the attraction of the scale insect males or the bug. The catch ofM. josephi males did not differ significantly among traps of different color, and was significantly higher with traps attached to the tree trunk than those suspended between trees. Comparison of the catch ofM. josephi among the three forests and between pine species suggests that the level of infestation ofPinus halepepsis andPinus brutia ssp.brutia is similar, despite the fact that the latter pine is resistant to the scale insect. Both sexes ofE. hebraicus were trapped in much lower numbers at the more infested sites. This may be related to interference with the activity ofE. hebraicus due to deterioration and drying of parts of the tree crowns and heavy colonization by generalist predators in injured trees.     

On detecting co-resident cloud instances using network flow watermarking techniques

Virtualization is the cornerstone of the developing third-party compute industry, allowing cloud providers to instantiate multiple virtual machines (VMs) on a single set of physical resources. Customers utilize cloud resources alongside unknown and untrusted parties, creating the co-resident threat—unless perfect isolation is provided by the virtual hypervisor, there exists the possibility for unauthorized access to sensitive customer information through the exploitation of covert side channels. This paper presents co-resident watermarking, a traffic analysis attack that allows a malicious co-resident VM to inject a watermark signature into the network flow of a target instance. This watermark can be used to exfiltrate and broadcast co-residency data from the physical machine, compromising isolation without reliance on internal side channels. As a result, our approach is difficult to defend against without costly underutilization of the physical machine. We evaluate co-resident watermarkingunder a large variety of conditions, system loads and hardware configurations, from a local laboratory environment to production cloud environments (Futuregrid and the University of Oregon’s ACISS). We demonstrate the ability to initiate a covert channel of 4 bits per second, and we can confirm co-residency with a target VM instance in $<$ 10 s. We also show that passive load measurement of the target and subsequent behavior profiling is possible with this attack. We go on to consider the detectability of co-resident watermarking, extending our scheme to create a subtler watermarking attack by imitating legitimate cloud customer behavior. Our investigation demonstrates the need for the careful design of hardware to be used in the cloud.